Process for obtaining seychellene

ABSTRACT

Process for obtaining Scychellene by heating a 1,2,3,6-tetramethyltricyclo 5,4,0,0(3,9)!undecan-2-ol with sodium acetate in glacial acetic acid. if the web.

United States Patent 3,839,476 PROCESS FOR OBTAINING SEYCHELLENE Georg Frater, Greifensee, Switzerland, assignor to Hofimann-La Roche Inc., Nutley, NJ. No Drawing. Filed July 16, 1973, Ser. No. 379,865 Int. Cl. C07c 13/54 US. Cl. 260-666 PY 2 Claims ABSTRACT OF THE DISCLOSURE Process for obtaining Seychellene by heating a 1,2,3,6 tetramethyltricyclo[5,43,0 1undecan-Z-ol with sodium acetate in glacial acetic acid.

BACKGROUND OF THE INVENTION This application relates to a process for obtaining Seychellene, which is a Z-methylene-3,6,8-trimethyl-tricyclo[5,3,1,0 ]undecane of the formula:

3 c cn ri e 73 Seychellene is a constituent of patchouli oil, which is used in perfume compositions and in flavoring compositions. Seychellene is of particular usefulness in perfumes. However, previously known syntheses have been somewhat un satisfactory for providing Seychellene of perfume grade.

SUMMARY OF THE INVENTION In accordance with this invention, Seychellene is obtained by heating a mixture comprising a l,2,3,6-tetramethyl-tricyclo[5,43,0 1 undecan-Z-ol of the formula:

II sodium acetate and'glacial acetic acid.

DETAILED DESCRIPTION OF THE INVENTION In the pictorial representation of the compounds given throughout this application, a thickened tapered line V indicates a substituent which is in the fl-orientation (above the plane of the molecule), and a dotted line indicates a substituent which is in the ot-orientation (below the plane of the molecule). It is to be understood that the pictorial representations of the compounds given throughout the specification are set forth for convenience and are to be construed as inclusive of other forms, including enantiomers and racemates and are not to be construed as limited to the particular form shown.

The process of this application can be carried out merely by heating a mixture containing the tetramethylundecan-2-ol of formula II, sodium acetate and glacial acetic acid. In this reaction, temperature and pressure are not critical, and temperatures of C. to 150 C. and atmospheric pressure can be suitably utilized. Preferably, a temperature of 80 C. to 118 C. is utilized in this reaction. If desired, this reaction can be carried out in a conventional inert organic solvent, such as hexane, methylenchlorid, benzene etc. However, it is preferred to carry "ice out this reaction utilizing the glacial acetic acid as the solvent medium, with sufficient glacial acetic acid being utilized to dissolve the sodium acetate and the tetrameth yl-undecan-Z-ol of formula II. In this reaction, the ratio of reactants in the reaction mixture is not critical. Preferably from about 0 to 4 parts by weight of sodium acetate and from about 2 to 10 parts by Weight of glacial acetic acid are utilized per part by weight of tetramethyl-undecan-Z-ol of formula II.

The tetramethyl-undecan-Z-ol of formula II can be obtained from a 1,3,6-trimethyl-tricyclo[5,4,0,0 ]undeca- 5,l0-dien-2one of the formula:

III

The tetramethyl-undecan-Z-ol of formula II is obtained by first hydrogenating the trimethyl-undeca-S,10-dien-2- one of formula III to form a mixture of cis and trans 1,3,6 trimethyl-tricyclo[5,4,0,0 ]undecan-2-oue isomers said isomers having the formulae:

The trans trimethyl-undecan-Z-one isomer of formula V is then converted to the tetramethyl-undecan-Z-ol of formula II by treatment thereof with methyl lithium.

The hydrogenation of the trimethyl-undecan-S,10-dien- 2-one of formula III can be carried out in a conventional manner in an inert organic solvent in the presence of a hydrogenation catalyst.

The treatment of the trans trimethyl-undecan-Z-one isomer of formula V with methyl lithium can be carried out in a conventional manner in an inert organic solvent. When a mixture of the isomers of the formulae IV and V is used in this reaction step, the corresponding 6-cis isomer is also formed having the formula:

In forming Seychellene in accordance with the process of this application from the trimethyl-undecan-S,10-dien- 2-one of formula III, it is not necessary to isolate the isomer intermediates of formulae II and V as pure materials. The tetramethyl-undecan-Z-ol of formula II can be suitably formed by treating a mixture of cis and trans trimethyl-undecan-2-one isomers of formulae IV and V with methyl lithium. Furthermore, the tetramethyl-undecan-2-ol of formula II can be suitably converted to Seychellene if it is in admixture with the tetramethyl-undecan- 2-01 of formula VI and the ketones of formulae IV and V, and such a mixture can be used in the process of this application without further working-up.

Since the trimethyl-undeca-S,10-dien-2-one of formula III is accessible in a simple manner and in good yields [see Helv. Chim. Acta, vol. 55, page 528 (1972)], the aforementioned mixture of compounds of formulae II, IV, V and VI constitutes a preferred starting material for conversion to Seychellene, in accordance with this application.

The examples which follow further illustrate this invention.

Example 1 A 1 molar solution of 2,6-dimethylphenol in benzene was treated with sodium hydride, and, after the termination of the hydrogen evolution, the mixture was treated with a 10% molar excess of 3-methyl-penta-2,4-dienyl-1- bromide. After stirring overnight at -5 C., the mixture was taken up in diethyl ether and extracted by shaking with water, with 10% aqueous potassium hydroxide solution and again with water. The dried organic phase contained 6-(3-methyl-penta-2,4-dienyl)-2,6-dimethyl-cyclohexa-2,4-dien-1-one; 80-90% yield. The dienone could be stored in solution at -10 C. but was unstable in concentrated form and at high temperatures. [U.V. in nhexane: maxima at 2300 A. e=2200) and 3050 A. (e'=4270)].

Example 2 5 g. of 6-(3-methyl-penta-2,4-dienyl)-2,6-dimethyl-cyclohexa-2,4-dien-1-one was dissolved in 25 ml. of benzene and treated with 5 g. of 2,6-dimethylphenol. The mixture was heated for 6 hours under reflux. After cooling to room temperature (22 C.), the mixture was extracted by shaking portionwise with a solution of 35 g. of potassium hydroxide, 25 ml. of water and 100 ml. of methanol. The organic phase was concentrated and the residue dis tilled at 7090 C./0.03 mm. Hg. The distillate contained 1,3,6-trimethy1-tricyclo[5,4,0,0 ]undeca-5,10-dien- 2-one and 1,3,6-trimethyl-tricyclo[5,3,1,0 ]undeca-5,9- dien-Z-one in the approximate molar ratio of 3:1.

This 3:1 mixture was dissolved in the same parts by volume of hexane and cooled to '30 C. The first mentioned ketone (the undeca-5,10-dien-2-one) precipitated out to a large extent. Concentration of the filtrate and repetition of this operation yielded a further amount of the crystalline ketone (the undeca-5,10-dien-2-one). The composition of the mixture of the aforementioned ketones thus changed from 3:1 parts by volume to about 1:3 parts by volume. The final separation of the ketones was carried out using hexane/ethyl acetate (8:2 parts by volume). There was thus obtained 1,3,6-trimethyl-tricyclo[5,4,0,0 ]undeca-5,10-dien-2-one, of melting point 5455 C., and 1,3,6-trimethyl-tricyclo[5,3,1,0 ]undeca-5,9-dien-2- one, of boiling point 70-75 C./0.03 mm. Hg.

Example 3 27 g. of 1,3,6-trimethyl-tricyclo[5,4,0,0 ]undeca-5,10- dien-2-one was hydrogenated in 200 ml. of methanol with 3 g. of 10% Pd/ C catalyst. After 4.5 hours, the reduction ended with the absorption of 2 mol of hydrogen. The mixture was worked up by chromatography on silica gel. 27 g. of a mixture of isomers of 1,3,6-trimethyl-tricyclo- [5,4,0,0 ]undecan-2-one was obtained, having a boiling point of 80-85 C./0.03 mm. Hg. Gas chromatography showed the mixture to be 65.5% by wt. of 6-cis isomer and 34.5% by Wt. of 6-trans isomer.

Example 4 The 27 g. mixture of ketone diastereomers, prepared in Example 3, was dissolved in 200 ml. of diethyl ether, and treated dropwise at 5 C. with 50 ml. of a ca 2-N solution of methyl lithium in diethyl ether. Then, the mixture was stirred for 2 hours at 5 C. The excess methyl lithium was subsequently decomposed with a small amount of ethanol, the mixture was poured onto water, and the aqueous phase was extracted with diethyl ether. After drying and evaporating the ethereal extract, the residual, colorless oil was distilled in a bulb tube at 90" C./0.03 mm. Hg. There was obtained 27 g. of a product which was shown by gas chromatographic analysis to be a mixture consisting of 64.4% wt. of unchanged cisketone, 0.5% by wt. of unchanged trans-ketone, 1.1% by wt. of 1,2,3,G-tetramethyl-tricyclo[5,4,0,0 undecan-Z-ol (6-cis isomer) and 34% by wt. of 1,2,3,6-tetramethylricyclo [5 ,4,0,0 undecan-Z-ol (6-trans isomer).

Example 5 The 27 g. mixture, obtained by the procedure of Example 4, was heated at C. for 20 hours with 45 g. of sodium acetate in 300 ml. of glacial acetic acid. Then, the mixture was poured onto 2 liters of water and extracted with pentane. The organic phase was washed neutral, dried and evaporated. The residual oil was chromatographed on 750 g. of silica gel with pentane/diethyl ether (9:1 parts by volume). There was obtained 8.6 g. of hydrocarbon fraction, consisting of 57.5% by wt. of (:)-seychellene and 39.5% by wt. and 3% by wt. of two unidentified compounds, and 16 g. of ketone fraction, consisting of 98.5% by wt. of 1,3,6-trimethyltricyclo[5,4,0,0 ]undecan-Z-one (6-cis isomer) and 1.5% by wt. of 1,3,6-trimethyl-tricyclo[5,4,O,0 ]undecan-Z-one (6-trans isomer).

The hydrocarbon fraction was separated on 170 g. of silica gel impregnated with 10% by wt. silver nitrate. The mixture was applied with pentane. Elution was carried out initially with pentane. Then 4.9 g. of i)-seychellene was eluted with pentane/diethyl ether (1:1 parts by volume); boiling point C./l2 mm. Hg.

I claim:

1. A process for producing a 2-methylene-3,6,8-trimethyl-tricycle[5,3,1,0 ]undecane of the formula:

comprising heating at a temperature from 20 C. to C., a mixture containing a 1,2,3,6-tetramethyl-tricyclo- [5,4,0,0 ]undecan-2-ol of the formula:

References Cited UNITED STATES PATENTS 2,972,635 4/1961 Booth 260-666 R 3,621,010 ll/1971 Rachlin 260-6755 VERONICA OKEEFE, Primary Examiner U.S. Cl. X.R. 260-6755 UNITED STATES PATENT OFFICE CERTHHCATE OF CORRECTHJN PATENT NO. I 3 839 L 76 DATED October 1, 197A INVENTOR(S) Georg Prater,

Hiscmflfiedmatmmrammaminmeamwe-memfiwdpamntmdflwtsmdLefiasPamm amhmwymnmwdasmwnmmw In column 1, "Foreign Application Priority Data" July 25, 1972 Switzerland 11093/72 should be inserted.

Signed and Sealed this ninth D 3} of December I 975 [SE AL] Arrest:

RUTH C. MASON C. MARSHALL DANN es g Offic Commissioner oflatents and Trademarks 

